Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study

J Infect Dis. 2022 May 4;225(9):1513-1520. doi: 10.1093/infdis/jiaa406.

Abstract

Background: We report long-term safety and immunogenicity of Takeda's tetravalent dengue vaccine candidate (TAK-003) in healthy children and adults living in dengue-endemic areas in Puerto Rico, Columbia, Singapore, and Thailand.

Methods: In part 1 of this phase 2, randomized, placebo-controlled trial we sequentially enrolled 1.5-45 year olds (n = 148) into 4 age-descending groups, randomized 2:1 to receive 2 doses of TAK-003 or placebo 90 days apart. In part 2, 1-11 year olds (n = 212) were enrolled and randomized 3:1 to TAK-003 or placebo groups. We assessed neutralizing antibody titers for the 4 dengue serotypes (DENV) up to month 36 in part 1, and symptomatic dengue and serious adverse events (SAEs) up to month 36 in both parts.

Results: At month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported.

Conclusions: The trial demonstrated persistence of neutralizing antibody titers against TAK-003 over 3 years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated.

Clinical trials registration: NCT01511250.

Keywords: dengue; immunogenicity; persistence; safety; vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Child
  • Dengue Vaccines*
  • Dengue Virus*
  • Dengue*
  • Humans
  • Immunogenicity, Vaccine
  • Vaccines, Attenuated
  • Vaccines, Combined

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated
  • Vaccines, Combined

Associated data

  • ClinicalTrials.gov/NCT01511250